ACEA Biosciences Presents Efficacy and Safety Data From AC0010 Phase I/II Clinical Trial for Treatment of Advanced Non-Small Cell Lung Cancer at the WCLC 2016 Conference

Novel EGFR tyrosine kinase inhibitor AC0010 displays high efficacy, tolerability, and safety in phase I/II clinical trials.

ACEA Biosciences, Inc. presented today updated efficacy and safety data from its phase I/II dose escalation and expansion clinical trial for its lead drug candidate, AC0010, at the World Conference on Lung Cancer (WCLC) 2016 in Vienna, Austria. The purpose of the trial was to determine the safety, antitumor activity, and recommended phase II dosage of AC0010 in T790M‐postitive non-small cell lung cancer (NSCLC) patients after treatment with first generation EGFR tyrosine kinase inhibitors (TKIs) have failed to produce a durable response.

AC0010 is an orally available, irreversible small molecule tyrosine kinase inhibitor in development for the treatment of patients with EGFRmut-positive NSCLC. It was designed specifically to inhibit epidermal growth factor receptor (EGFR) active mutations (L858R, Exon 19 del) and the T790M acquired resistance mutation.

“Based on AC0010’s encouraging efficacy, tolerability, and distinct safety profile, it appears that this novel compound may provide an important treatment option for NSCLC patients who carry the EGFR T790M-positive resistance mutation,” said lead investigator of the trial Dr. Yi-Long Wu, MD, of the Guangdong Lung Cancer Institute, Guangdong General Hospital (GGH), and Guangdong Academy of Medical Sciences in Guangzhou, China. “Based on the good efficacy and tolerability, a 300 mg BID dose was selected as the RP2D.”

“About 1.8 million new patients are diagnosed with lung cancer every year and, amongst these, 15-40% develop EGFR mutations. Considering these sobering numbers, we are very pleased with the preliminary efficacy and safety data for AC0010. The results presented today make us optimistic that further clinical trials of AC0010 as a treatment option for patients with advanced NSCLC is highly justified. We have initiated two registration trials in China, as well as a multicenter open-label phase I/II trial in the USA,” said Dr. Xiao Xu, President and CEO of ACEA Biosciences. “We will continue to work closely with patients, investigators, and regulatory agencies around the world to bring this important treatment option to NSCLC patients.”

In the study presented at WCLC, oral AC0010 was administered on a 28‐day cycle with a starting dose of 50 mg twice per day (BID). In any given dose regimen, if 1 out of 3 patients demonstrated a partial response within the first cycle, and no dose-limiting toxicity was determined, up to 20 patients were subsequently enrolled. Plasma samples were collected to evaluate the pharmacokinetics of AC0010, and the presence of the T790M mutation in biopsy samples was evaluated by a central laboratory. The primary efficacy outcome measures for this analysis were objective response rate (ORR) and disease control rate (DCR), as assessed by the investigator according to RECIST v.1.1.

Summary of Efficacy Data
Using the international rules for Response Evaluation Criteria in Solid Tumors (RECIST) responses were observed at all dose levels except 50 mg BID. Amongst 158 patients evaluated in all regimens, the ORR (including unconfirmed responses) was 42%. In the dose cohorts between 200 mg BID and 300 mg BID (n=103 pts), the ORR and DCR were 50% and 90%, respectively. At 300 mg BID, which was selected as RP2D, a total of 48 patients were treated and the ORR and DCR were 52% and 94%, respectively. Pharmacokinetic analyses demonstrate rapid absorption with a Tmax of 2­4 hours and a median T1/2 of 7-8 hours.

Summary of Safety Data
As of 28 Oct 2016, 158 patients have been treated across 7 drug regimens (50, 100, 150, 200, 250, 300, and 350 mg BID). At the 28 Oct 2016 cutoff, 158 patients were evaluable. Maximum Tolerated Dose (MTD) has not been reached. The most common adverse events (AE) regardless of study drug relationship were diarrhea (43%), rash (28%), and ALT/AST elevation (44%/41%). Most AEs were grade 1 and 2. The most common Grade 3/4 drug related AEs were diarrhea (1%), rash (1%), and ALT/AST elevation (5%, 3%). All patients with grade 3/4 AEs recovered after either stopping the treatment or reducing the dose. As of the cutoff date, no cases of Grade 2/3 hyperglycemia were observed, and no patients had AEs leading to death.

About AC0010
AC0010 is a pyrrolopyrimidine-based irreversible inhibitor of the EGFR tyrosine kinase which is in development for the treatment of NSCLC. Structurally distinct from previously reported pyrimidine-based irreversible EGFR inhibitors such as Osimertinib, AC0010 selectively inhibits EGFR active and T790M mutations up to a 298-fold more efficiently than wild-type EGFR. Multiple clinical trials currently underway in China and the USA are demonstrating the utility of AC0010 in this patient population. ACEA holds worldwide rights for AC0010.

About ACEA Biosciences
ACEA Biosciences, Inc. (ACEA) is a privately owned biotechnology company focused on the development and commercialization of innovative cell analysis instrumentation for life sciences, and on the discovery and development of novel pharmaceutical products for the treatment of chronic diseases. ACEA’s instruments, xCELLigence® and NovoCyte™, are used in preclinical drug discovery and development, toxicology, safety pharmacology, disease studies, and basic academic research. More than 1,700 instruments have been placed globally, leading to >1,250 peer-reviewed publications from both academia and the pharmaceutical industry in diverse applications spanning everything from cancer immunotherapy and cardiotoxicity to chemotactic migration and GPCR inhibition. ACEA has leveraged its technology platform to develop a robust pipeline of clinical and preclinical small molecules for the treatment of cancer and autoimmune diseases, with two clinical stage programs running in China and the USA. ACEA Biosciences is headquartered in San Diego, California with world-class manufacturing operations in Hangzhou, China.